Progress and impact of enzyme measurement standardization

Area of Science:

• Clinical Chemistry
• Laboratory Medicine
• Enzyme Assays

Background:

• The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) provides reference measurement procedures (RMPs) for key enzymes.
• Traceability of commercial calibrators to RMPs is essential for consistent results across different laboratories and methods.
• Current standardization efforts for many enzyme assays remain insufficient, impacting clinical diagnostics.

Purpose of the Study:

• To assess the current state of standardization for common enzyme measurements in clinical laboratories.
• To identify specific enzymes lacking adequate traceability and highlight areas for improvement.
• To propose strategies for achieving better standardization in clinical enzymology.

Main Methods:

• Review of existing IFCC reference measurement procedures (RMPs).
• Analysis of the traceability of commercial enzyme assays to RMPs.
• Evaluation of analytical performance and standardization status of various enzyme assays, including creatine kinase (CK), γ-glutamyltranspeptidase (GGT), aminotransferases, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and α-amylase (AMY).

Main Results:

• Creatine kinase (CK) measurements are satisfactorily standardized.
• Significant improvements observed in γ-glutamyltranspeptidase (GGT) assay performance.
• Aminotransferase assays often exceed desirable performance due to lack of pyridoxal-5-phosphate. Lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and α-amylase (AMY) assays show major disagreements, indicating poor traceability.
• Some manufacturers still market assays not traceable to international RMPs, and end-users continue using substandard assays.

Conclusions:

• Achieving standardization in clinical enzymology requires improved implementation of traceability to higher-order references, particularly for LDH, ALP, and AMY.
• Addressing analytical selectivity differences in enzyme assays is critical.
• Defining clinically acceptable measurement uncertainty, using commutable materials in External Quality Assessment Schemes (EQAS), and employing trueness-based evaluation are key strategies for future standardization.